ton rullmann
ton rullmann
| My PhD research revolved around computer simulations of the interaction between molecules (small organic compounds, enzyme active sites) and their surroundings, in particular water. Later I worked on interactions between protein and DNA molecules, trying to find clues for how proteins involved in regulation of gene expression recognize the specific DNA site they bind to. All these problems relate to a single fundamental question: how do biological systems function despite the fact that all components are moving and turning all the time, or even exchanging positions? Is it possible to describe how thousands or millions of moving particles can form an organized system such as a large protein molecule or a cell? | Computer simulations provide fascinating opportunities to mimick such systems in a myriad number of ways. I have used Molecular Dynamics techniques to look at the equilibrium structure of proteins and protein-DNA complexes, and I have used Monte Carlo techniques to calculate the effect of water on a very simple chemical reaction, the addition of a proton. |
| Inspired by the work of several scientists who tried to understand how complex order arises out of molecular chaos, I formulated ideas for building models of systems that might resemble evolving cells (•Information processing based cell model and •From Abstract Chemistry to Biology). | |
| •PhD thesis •Publication list | Keywords: •artificial life, •molecular dynamics, •statistical mechanics, •order out of chaos, •emergence. |
| After that, it was time to do something else - like working in the real world of industrial projects and practical applications, and learning about interactions between people. | |
| In being in the world and interacting with people, the question "why" something happens is less useful than the question "how" it happens. "What is going on right now" and "how does the world appear to me right now" are key questions to orient ourselves. This awareness of here-and-now is an important ingredient of gestalt therapy. The gestalt therapeutic model — a model of ´Excitement and Growth in the Human Personality´, the subtitle of the classic 1951 book on gestalt therapy by Perls, Hefferline and Goodman — has become more and more important to me. Gestalt has taught me to be less of a spectator, studying systems from a distance, and more of a participant, that is learning by doing and interacting. In some sense the experiential and experimental approach of gestalt therapy is not so different from true scientific inquiry. Except, I´m now part of the game myself! Taking part and trusting the flow of actions and emotions is ultimately more rewarding than trying to ´know it all´. Manipulation does not pay off, but truly acknowledging our mutual needs and capabilities does. | Keywords: •gestalt therapy, •Fritz Perls, •paradoxical theory of change, •organismic self-regulation. |
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•Gestalt section of this site •Dutch gestalt links •Association for the Advancement of Gestalt Therapy •Gestaltcentrum De Walvis |
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| Studying, thinking about and participating in living systems has made it increasingly clear to me that we may never fully know any of them. Theories and computer models can be poor or good mimics of the actual system — they may be beautiful to look at, and can be an excellent showpiece in your living room or in the library — but they are not the real thing. The model is a new system in itself, having its own quirks and bad manners, as any computer modeller can tell you. Each living system seems to have a life, or mind, of its own. This I call ´mind in matter´. | |
| Finally: how do we view ourselves? Does the mechanistic picture that modern science is painting of our own bodies capture all of our reality? The new systems view in biology at least tries to overcome some of the limitations of a reductionist approach, in which a body is nothing but the sum of its parts. Will it go far enough? Are we capable of reconciling the mechanistic view with the participatory view that our human experience is telling us is required to survive as a person and maybe as a species as well? How do we do justice to all of life, to all mind? |
These themes are discussed more extensively in the Mind & Matter section of this site, in particular in
"Met open ogen — over wetenschap en onze kijk op de wereld" (in Dutch). In the Personal Health section I write about these themes in relation to the practical application of medical and pharmaceutical research. •Mind & Matter section •"Met open ogen" (pdf) •Personal Health section |
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I am project leader for the collaboration between •MSD
and •Entelos on the RA PhysioLab platform,
a large scale mathematical model of the joint of a rheumatoid arthritis (RA) patient.
The platform is used to simulate the effect of treatments on the disease process, at the level of
molecular, cellular and clinical characteristics. We use the platform to help develop new therapies
for rheumatoid arthritis.
The other part of my work involves analysis of gene expression patterns due to effects of disease or drug treatment. Modern •microarray technologies and •statistical analysis tools make it possible to analyze the expression characteristics of all genes in a cell at the same time, thus giving a view on the cell as an integrated system. I am also working on statistical analysis of protein expression measurements, and I am coordinating a number of projects that aim to decipher biological effects by simultaneously measuring many •metabolites in the blood of animals or patients. |
| Comprehensive measurements of gene expression (genomics), protein concentrations (proteomics) and metabolite levels (metabolomics), together with pattern analysis and simulations at various levels of detail (of which PhysioLab is only one example) constitute the rapidly expanding field of systems biology: the understanding of biological systems, from cells to organisms, as functioning networks and integrated wholes rather than isolated components. |
| Keywords: •systems biology, •computational physiology, •clinical trial simulation, •virtual patients. •pharmacogenomics. |
